Contributions to Hypertension With Androgen Deprivation Therapy

Phase 4

Recruiting

• Conditions: Androgen Deprivation Therapy; Autonomic Dysfunction; Renal Disease; Hypertension; Prostate Cancer
• Interventions: Drug: Gonadotropin Releasing Hormone Agonists (GNRH); Drug: Placebo; Drug: Androgen receptor (AR) inhibitor

• Registration Number: NCT05700903
• Lead Sponsor: University of Colorado, Denver

Brief Summary

This study plans to learn more about contributors to high blood pressure in men who undergo androgen deprivation therapy (ADT) to treat prostate cancer. Prostate cancer is the most common non-skin cancer in men, affecting approximately 1 in 8 American men and its primary treatment is through the use of ADT. However, ADT increases the likelihood of developing heart disease including high blood pressure. This study will determine if dysfunction of the nervous system and/or kidneys occurs in men undergoing ADT, as these systems play a significant role in control of blood pressure. The results from this study will help us understand the ways in which ADT contributes to heart disease and help us develop therapies to prevent heart disease in prostate cancer survivors.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-01-10
• Study First Submitted QC: 2023-01-18
• Study First Posted: 2023-01-26
• Study Start: 2023-09-20
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-10
• Last Update Posted: 2024-06-12
• Primary Completion: 2028-03-31
• Study Completion: 2028-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 228

Inclusion Criteria

• -age 40+ years;
• resting blood pressure <140/90 mmHg;
• fasted blood glucose <126 mg/dL;
• testosterone ≥400 ng/dL;
• sedentary to recreationally active;
• nonsmokers;
• healthy as determined by medical history, physical exam, blood and urine chemistries and resting and exercise ECG during a physician supervised graded exercise treadmill test OR recent diagnosis of non-metastatic prostate cancer with plans to undergo androgen deprivation therapy;
• PSA <4.00 ng/dL if in the non-cancer group;
• Gleason Score ≤7 if in the prostate cancer group;
• no use of medications that might influence cardiovascular function (e.g., antihypertensives, lipid-lowering medications);
• willing and able to be on GnRHagonist and AR inhibitor;
• not taking antioxidant vitamins, corticosteroids, or anti-inflammatory medications, or willing to stop use for four weeks prior to the start of the study;
• not using exogenous sex hormones for at least one year

Read More

Exclusion Criteria

• -acute liver disease;
• chronic kidney disease, serum creatinine >1.3 mg/dL, macroalbuminuria >300 mg/g of proteinuria
• pre-existing or active cardiac, renal or hepatic disease, epilepsy or other seizure disorder;
• diabetes, active or chronic infection, disease that affects the nervous system;
• Gleason Score ≥8;
• thyroid dysfunction, defined as ultrasensitive TSH <0.5 or >5.0 mU/L, volunteers with abnormal TSH values will be re-considered for participation after follow-up evaluation by the PCP with initiation or adjustment of thyroid hormone replacement;
• tobacco use within the previous 12 months

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prostate Cancer	Gonadotropin Releasing Hormone Agonists (GNRH)	Men undergoing androgen deprivation therapy via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for the treatment of prostate cancer
Healthy + Placebo	Placebo	Healthy men undergoing placebo for 9 weeks.
Prostate Cancer	Androgen receptor (AR) inhibitor	Men undergoing androgen deprivation therapy via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for the treatment of prostate cancer
Healthy + ADT	Gonadotropin Releasing Hormone Agonists (GNRH)	Healthy men undergoing gonadal suppression via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for 9 weeks
Healthy + ADT	Androgen receptor (AR) inhibitor	Healthy men undergoing gonadal suppression via gonadotropin releasing hormone agonist plus androgen receptor inhibitor for 9 weeks

Primary Outcome Measures

Name	Time	Method
Change in Cardiovagal Baroreflex Sensitivity	Before and after 9 weeks of androgen deprivation therapy or placebo	The change in cardiovagal baroreflex sensitivity will be assessed the modified Oxford procedure
Change in blood pressure reactivity to the cold pressor test	Before and after 9 weeks of androgen deprivation therapy or placebo	The change in blood pressure will be assessed from quiet rest to sympathetic activation using the cold pressor test
Change in beat-to-beat blood pressure variability	Before and after 9 weeks of androgen deprivation therapy or placebo	Beat-to-beat blood pressure variability will be using finger photoplethysmography measured in the laboratory.
Change in exercise pressor reflex	Before and after 9 weeks of androgen deprivation therapy or placebo	The change in blood pressure will be assessed from quiet rest to isometric handgrip exercise
Change in renal vascular resistance	Before and after 9 weeks of androgen deprivation therapy or placebo	Renal blood flow will be determined using ultrasound and blood pressure will be determined using finger photoplethysmography. These measures will be used to estimate renal vascular resistance.
Change in ambulatory blood pressure variability	Before and after 9 weeks of androgen deprivation therapy or placebo	Ambulatory blood pressure variability will be determined from 24-hour ambulatory blood pressure monitoring.
Change in Renal dysfunction biomarkers	Before and after 9 weeks of androgen deprivation therapy or placebo	Neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule (KIM)-1, interleukin (IL)-18, and vanin-1 will be quantified in urine using commercially available assay kits. Concentrations will be normalized to urinary flow rate.

Secondary Outcome Measures

Name	Time	Method
Change in Sympathetic reactivity	Before and after 9 weeks of androgen deprivation therapy or placebo	The change in muscle sympathetic nerve activity will be assessed from quiet rest to sympathetic activation using the cold pressor test.
Change in sympathetic baroreflex sensitivity	Before and after 9 weeks of androgen deprivation therapy or placebo	Changes in muscle sympathetic nerve activity in response to changes in blood pressure will be assessed using the modified Oxford procedure
Change in glomerular filtration rate	Before and after 9 weeks of androgen deprivation therapy or placebo	Glomerular filtration rate and renal plasma flow will be calculated by iohexol (Omnipaque 300, GE Healthcare) clearance technique. Plasma and urine iohexol and p-aminohippurate clearance will be measured on a High-Performance Liquid Chromatography (HPLC, Waters, Milford, MA).
Change in renal plasma flow	Before and after 9 weeks of androgen deprivation therapy or placebo	Renal plasma flow will be calculated by p-aminohippurate (Basic Pharma) clearance techniques. Plasma and urine p-aminohippurate clearance will be measured on a High-Performance Liquid Chromatography (HPLC, Waters, Milford, MA).

Trial Locations

Locations (1)

UCHealth University of Colorado Hospital; 🇺🇸 Aurora, Colorado, United States